1. Field of the Invention
The present invention relates generally to apparatus and methods for inhibiting restenosis in blood vessels following angioplasty or other intravascular procedures for treating atherosclerosis and other diseases of the vasculature. More particularly, the present invention provides improved apparatus and methods for cryogenically treating a lesion within a patient""s vasculature to inhibit hyperplasia (which often occurs after intravascular procedures).
A number of percutaneous intravascular procedures have been developed for treating atherosclerotic disease in a patient""s vasculature. The most successful of these treatments is percutaneous transluminal angioplasty (PTA). PTA employs a catheter having an expansible distal end, usually in the form of an inflatable balloon, to dilate a stenotic region in the vasculature to restore adequate blood flow beyond the stenosis. Other procedures for opening stenotic regions include directional arthrectomy, rotational arthrectomy, laser angioplasty, stents and the like. While these procedures, particularly PTA and stenting, have gained wide acceptance, they continue to suffer from the subsequent occurrence of restenosis.
Restenosis refers to the re-narrowing of an artery within weeks or months following an initially successful angioplasty or other primary treatment. Restenosis typically occurs within weeks or months of the primary procedure, and may affect up to 50% of all angioplasty patients to some extent. Restenosis results at least in part from smooth muscle cell proliferation in response to the injury caused by the primary treatment. This cell proliferation is referred to as xe2x80x9chyperplasia.xe2x80x9d Blood vessels in which significant restenosis occurs will typically require further treatment.
A number of strategies have been proposed to treat hyperplasia and reduce restenosis. Previously proposed strategies include prolonged balloon inflation, treatment of the blood vessel with a heated balloon, treatment of the blood vessel with radiation, the administration of anti-thrombotic drugs following the primary treatment, stenting of the region following the primary treatment, and the like. While these proposal have enjoyed varying levels of success, no one of these procedures is proven to be entirely successful in avoiding all occurrences of restenosis and hyperplasia.
It has recently been proposed to prevent or slow reclosure of a lesion following angioplasty by remodeling the lesion using a combination of dilation and cryogenic cooling. Co-pending U.S. patent application Ser. No. 09/203,011, filed Dec. 1, 1998, the full disclosure of which is incorporated herein by reference, describes an exemplary structure and method for inhibiting restenosis using a cryogenically cooled balloon. While these proposals appear promising, the described structures and methods for carrying out endovascular cryogenic cooling would benefit from still further improvements. In particular, work in connection with the present invention has shown that the antiproliferative efficacy of endoluminal cryogenic systems can be quite sensitive to the temperature to which the tissues are cooled.
Although cryogenic cooling shows great promise for endovascular use, it can be challenging to safely and reproducibly effect the desired controlled cooling. For example, many potential cryogenic fluids, such as liquid nitrous oxide, exhibit high levels of heat transfer. This is problematic as high cooling temperatures may kill the cooled cells (cell necrosis) rather than provoking the desired antiproliferative effect of endoluminal cryotherapy. Work in connection with present invention suggests that other cryogenic fluids, such as the AZ-50(trademark) fluorocarbons (which may exhibit more ideal temperature characteristics), may raise bio-compatibility and safety concerns. Additionally, improved safety measures to minimize any leakage of even biocompatible cryogenic fluids into the blood stream would be beneficial. Further, cryogenic systems that result in liquid vaporization within the balloon surface can decrease the temperature to which tissues are cooled and thus reduce the efficacy in inhibiting hyperplasia.
For these reasons, it would be desirable to provide improved devices, systems, and methods for treatment of restenosis and hyperplasia in blood vessels. It would be particularly desirable if these improved devices, systems, and methods were capable of delivering treatment in a very controlled and safe manner so as to avoid overcooling and/or injury to adjacent tissue. These devices, systems, and methods should ideally also inhibit hyperplasia and/or neoplasia in the target tissue with minimum side effects. At least some of these objectives will be met by the invention described herein.
2. Description of the Background Art
A cryoplasty device and method are described in PCT Publication No. WO 98/38934. Balloon catheters for intravascular cooling or heating a patient are described in U.S. Pat. No. 5,486,208 and PCT Publication No. WO 91/05528. A cryosurgical probe with an inflatable bladder for performing intrauterine ablation is described in U.S. Pat. No. 5,501,681. Cryosurgical probes relying on Joule-Thomson cooling are described in U.S. Pat. Nos. 5,275,595; 5,190,539; 5,147,355; 5,078,713; and 3,901,241. Catheters with heated balloons for post-angioplasty and other treatments are described in U.S. Pat. Nos. 5,196,024; 5,191,883; 5,151,100; 5,106,360; 5,092,841; 5,041,089; 5,019,075; and 4,754,752. Cryogenic fluid sources are described in U.S. Pat. Nos. 5,644,502; 5,617,739; and 4,336,691. A body cooling apparatus is described in U.S. Pat. No. 3,125,096. Rapid exchange catheters are described in U.S. Pat. Nos. 5,383,853 and 5,667,521. A MEINHARD(copyright) nebulizer is described at the following website: http://www.meinhard.com/product3.htm. The following U.S. Patents may also be relevant to the present invention: U.S. Pat. Nos. 5,458,612; 5,545,195; and 5,733,280.
The full disclosures of each of the above references are incorporated herein by reference.
The present invention provides improved devices, systems, and methods for inhibiting hyperplasia in blood vessels. The blood vessels will often be treated for atherosclerotic or other diseases by balloon angioplasty, arthrectomy, rotational arthrectomy, laser angioplasty, stenting, or another primary treatment procedure. Inhibition of excessive cell growth is desirable when such treatments are employed so as to reduce and/or eliminate any associated hyperplasia and to maintain the patency of a body lumen. The present invention allows for cryotherapy treatment of a target portion within the body lumen of a patient in a very controlled and safe manner, particularly when using fluid capable of cooling tissues below a target temperature range.
In a first aspect, the invention provides a cryotherapy catheter comprising a catheter body having a proximal end and a distal end with a cooling fluid supply lumen and an exhaust lumen extending therebetween. A first balloon is disposed near the distal end of the catheter body in fluid communication with the supply and exhaust lumens. A second balloon is disposed over the first balloon with a thermal barrier therebetween.
Treatment according to this first aspect of the present invention can be effected by positioning the first balloon within the blood vessel adjacent a target portion. The xe2x80x9ctarget portionxe2x80x9d will often be a length within the blood vessel which is at risk of hyperplasia, typically as a result of balloon angioplasty (or some other treatment). Cryogenic cooling fluid is introduced into the first balloon (in which it often vaporizes) and exhausted. The second balloon expands to radially engage the vessel wall. The target portion is cooled to a temperature which is sufficiently low for a time which is sufficiently long to inhibit excessive cell proliferation. Heat transfer will be inhibited between the first and second balloons by the thermal barrier so as to limit cooling of the target portion. The inhibited cooling treatment will be directed at all or a portion of a circumferential surface of the body lumen, and will preferably result in cell growth inhibition, but not necessarily in significant cell necrosis. Particularly in the treatment of arteries before, during, and/or following balloon angioplasty, cell necrosis may be undesirable if it increases the hyperplastic response. Thus, the present invention will cool target tissue to a limited cooling temperatures to slow or stop cell proliferation.
The thermal barrier may comprise a gap maintained between the balloons by a filament. The filament typically comprises a helically wound, braided, woven, or knotted monofilament. The thermal barrier may also comprise a gap maintained between the balloons by a plurality of bumps on an outer surface of the first balloon or an inner surface of the second balloon. Alternatively, the thermal barrier may comprise a sleeve. The sleeve can be solid or perforated. The catheter of the present invention may also be equipped with a guidewire lumen that extends axially outside the exhaust lumen to minimize the occurrence of cryogenic fluid entering the blood stream via the guidewire lumen.
Suitable cryogenic fluids will preferably be non-toxic and include liquid nitrous oxide, liquid carbon dioxide, and the like. The balloons are preferably inelastic and have a length of at least 1 cm each, more preferably in the range from 2 cm to 5 cm each. The balloons will have diameters in the range from 2 mm to 5 mm each in a coronary artery and 2 mm to 10 mm each in a peripheral artery. Generally, the temperature of the outer surface of the first balloon will be in a range from about 0xc2x0 C. to about xe2x88x9250xc2x0 C. and the temperature of the outer surface of the second balloon will be in a range from about xe2x88x923xc2x0 C. to about xe2x88x9215xc2x0 C. This will provide a treatment temperature in a range from about xe2x88x923xc2x0 C. to about xe2x88x9215xc2x0 C. The tissue is typically maintained at the desired temperature for a time period in the range from about 1 to 60 seconds, preferably being from 20 to 40 seconds. Hyperplasia inhibiting efficacy may be enhanced by repeating cooling in cycles, typically with from about 1 to 3 cycles, with the cycles being repeated at a rate of about one cycle every 60 seconds.
In another aspect, the invention provides a cryotherapy system comprising an elongate body having a proximal end and a distal end with a fluid supply and exhaust lumen extending therebetween. A first balloon defines a volume in fluid communication with the supply and exhaust lumens. A fluid shutoff is coupled to a cryogenic fluid supply with the supply lumen. A second balloon is disposed over the first balloon with a vacuum space therebetween. The vacuum space is coupled to the fluid shutoff so as to inhibit flow of cryogenic fluid into the first balloon in response to a change in the vacuum space.
Advantageously, the cryotherapy system can monitor the integrity of both balloons during cooling to ensure that no cryogenic fluid is escaping from the first balloon or blood entering from the second balloon. Further, in the event of a failure, the fluid shutoff can prevent the delivery of additional cryogenic fluid into the supply lumen while the second balloon acts to contain any cryogenic fluid that may have escaped the first balloon.
The fluid shutoff typically comprises a vacuum switch connected to a shutoff valve by a circuit, the circuit being powered by a battery. The switch may remain closed only when a predetermined level of vacuum is detected in the second balloon. The closed switch allows the shutoff valve (in fluid communication with the cryogenic fluid supply) to be open. Alternatively, the circuit may be arranged so that the switch is open only when the predetermined vacuum is present, with the shutoff valve being open when the switch is open. The vacuum is reduced when either the first balloon is punctured, allowing cryogenic fluid to enter the vacuum space, or the second balloon is punctured, allowing blood to enter the vacuum space. The vacuum may be provided by a simple fixed vacuum chamber coupled to the vacuum space by a vacuum lumen of the catheter body, or may be applied with a simple positive displacement pump, the pump optionally similar to a syringe. Still further vacuum means might be used, including cryogenic vacuum pumps and the like. The cryogenic fluid supply and battery may be packaged together in a detachable energy pack. A plurality of separate replaceable energy packs allow for multiple cryogenic fluid cooling cycles. The system may additionally comprises a hypsometer with a thermocouple, thermistor, or the like, located in the first balloon to determine the pressure and/or temperature of fluid in the first balloon.
In another aspect, the present invention provides a cryotherapy catheter comprising a catheter body having a proximal end and a distal end with a nebulizer disposed adjacent the distal end. A first balloon is disposed on the distal end of the catheter body. The inner surface of the first balloon is in fluid communication with the nebulizer.
The nebulizer may comprise at least one port in fluid communication with a liquid supply lumen and a gas supply lumen. The liquid supply lumen may further be coaxial with the gas supply lumen. Thus, the nebulizer can introduce a liquid and gas mixture into the first balloon so that pressure and the enthalpy of vaporization of a safe cryogenic fluid within the balloon surface can be independently selected and/or controlled. This in turn allows for improved temperature control of the cryogenic fluid.
Another aspect of the present invention is a method for treating a target portion of a blood vessel. The method comprises positioning a balloon within the blood vessel adjacent the target portion, introducing a cryogenic cooling fluid into the balloon, and exhausting the cooling fluid. The target portion is cooled to a temperature and for a time sufficient to inhibit subsequent cell growth. The blood vessel is a peripheral artery subject to hyperplasia resulting from a primary treatment. Suitable peripheral arteries which may benefit from these treatments include arteries of the legs, kidneys, renal, iliac, popliteal, and preferably superficial femoral arteries.
In yet another aspect, the invention provides a method for treating a target portion of a blood vessel. The method comprises positioning a first balloon within the blood vessel adjacent the target portion, introducing a cryogenic cooling fluid into the first balloon, and exhausting the cooling fluid. A second balloon disposed over the first balloon is expanded to radially engage the vessel wall. The target portion is cooled to a temperature and for a time sufficient to inhibit subsequent cell growth. Heat transfer between the first and second balloons is inhibited so as to limit cooling of the target portion.
In another aspect, the invention provides method for treating a target portion of a blood vessel. The method comprises positioning a first balloon within the blood vessel adjacent the target portion, introducing a cryogenic cooling fluid into the first balloon, and exhausting the cooling fluid. A second balloon disposed over the first balloon is expanded to radially engage the vessel wall. The target portion is cooled to a temperature and for a time sufficient to inhibit subsequent cell growth. Containment of the first and second balloons is monitored during cooling.
In another aspect, the invention provides a method for treating a target portion of a blood vessel. The method comprises positioning a balloon within the blood vessel adjacent the target portion, introducing a cryogenic liquid and gas mixture into the balloon with a nebulizer, and exhausting the cryogenic liquid and gas mixture. The target portion is cooled to a temperature and for a time sufficient to inhibit subsequent cell growth.